{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:43:45Z","timestamp":1790775825273,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic medication that has recently been approved for the treatment of obesity as well. Semaglutide is postulated to be a promising candidate for the treatment of non-alcoholic steatohepatitis (NASH). Here, Ldlr-\/-.Leiden mice received a fast-food diet (FFD) for 25 weeks, followed by another 12 weeks on FFD with daily subcutaneous injections of semaglutide or vehicle (control). Plasma parameters were evaluated, livers and hearts were examined, and hepatic transcriptome analysis was performed. In the liver, semaglutide significantly reduced macrovesicular steatosis (\u221274%, p &lt; 0.001) and inflammation (\u221273%, p &lt; 0.001) and completely abolished microvesicular steatosis (\u2212100%, p &lt; 0.001). Histological and biochemical assessment of hepatic fibrosis showed no significant effects of semaglutide. However, digital pathology revealed significant improvements in the degree of collagen fiber reticulation (\u221212%, p &lt; 0.001). Semaglutide did not affect atherosclerosis relative to controls. Additionally, we compared the transcriptome profile of FFD-fed Ldlr-\/-.Leiden mice with a human gene set that differentiates human NASH patients with severe fibrosis from those with mild fibrosis. In FFD-fed Ldlr-\/-.Leiden control mice, this gene set was upregulated as well, while semaglutide predominantly reversed this gene expression. Using a translational model with advanced NASH, we demonstrated that semaglutide is a promising candidate with particular potential for the treatment of hepatic steatosis and inflammation, while for the reversal of advanced fibrosis, combinations with other NASH agents may be necessary.<\/jats:p>","DOI":"10.3390\/ijms24108494","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T03:32:27Z","timestamp":1683689547000},"page":"8494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-\/-.Leiden Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3725-6785","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Inia","sequence":"first","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"},{"name":"Cardiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-6311","authenticated-orcid":false,"given":"Geurt","family":"Stokman","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-943X","authenticated-orcid":false,"given":"Martine C.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Worms","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-9037","authenticated-orcid":false,"given":"Lars","family":"Verschuren","sequence":"additional","affiliation":[{"name":"Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0248-4008","authenticated-orcid":false,"given":"Martien P. M.","family":"Caspers","sequence":"additional","affiliation":[{"name":"Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0724-0897","authenticated-orcid":false,"given":"Aswin L.","family":"Menke","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Petitjean","sequence":"additional","affiliation":[{"name":"PharmaNest Inc., Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-1830","authenticated-orcid":false,"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"PharmaNest Inc., Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Petitjean","sequence":"additional","affiliation":[{"name":"PharmaNest Inc., Princeton, NJ 08540, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Cardiology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"},{"name":"Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans M. G.","family":"Princen","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-8446","authenticated-orcid":false,"given":"Anita M.","family":"van den Hoek","sequence":"additional","affiliation":[{"name":"Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1016\/S1262-3636(08)73397-4","article-title":"Physiology of incretins (GIP and GLP-1) and abnormalities in type 2 diabetes","volume":"34","author":"Gautier","year":"2008","journal-title":"Diabetes Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molmet.2019.09.010","article-title":"Glucagon-like peptide 1 (GLP-1)","volume":"30","author":"Finan","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.2337\/dc12-2006","article-title":"Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M)","volume":"36","author":"Dimas","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.2337\/dc13-2760","article-title":"Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1)","volume":"37","author":"Wysham","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3389\/fendo.2019.00155","article-title":"The discovery and development of liraglutide and semaglutide","volume":"10","author":"Knudsen","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1111\/dom.12932","article-title":"Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity","volume":"19","author":"Blundell","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S2213-8587(18)30024-X","article-title":"Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): A randomised, open-label, phase 3b trial","volume":"6","author":"Pratley","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"258","DOI":"10.2337\/dc17-0417","article-title":"Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects with Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial","volume":"41","author":"Ahmann","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(21)00213-0","article-title":"Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial","volume":"397","author":"Davies","year":"2021","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1001\/jama.2021.1831","article-title":"Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults with Overweight or Obesity: The STEP 3 Randomized Clinical Trial","volume":"325","author":"Wadden","year":"2021","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1001\/jama.2021.23619","article-title":"Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity without Diabetes: The STEP 8 Randomized Clinical Trial","volume":"327","author":"Rubino","year":"2022","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S2213-8587(22)00008-0","article-title":"Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): A randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial","volume":"10","author":"Kadowaki","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/apt.16608","article-title":"Randomised clinical trial: Semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging","volume":"54","author":"Flint","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liang, W., Menke, A.L., Driessen, A., Koek, G.H., Lindeman, J.H., Stoop, R., Havekes, L.M., Kleemann, R., and Van den Hoek, A.M. (2014). Establishment of a General NAFLD Scoring System for Rodent Models and Comparison to Human Liver Pathology. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115922"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/ijo.2016.74","article-title":"Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR\u2212\/\u2212.Leiden mice","volume":"40","author":"Morrison","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jcmgh.2017.10.001","article-title":"Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model","volume":"5","author":"Verschuren","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/hep4.1270","article-title":"Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-\/-.Leiden Mice","volume":"2","author":"Morrison","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/hep.32427","article-title":"Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles","volume":"76","author":"Bruzzone","year":"2022","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Van den Hoek, A.M., Verschuren, L., Worms, N., Van Nieuwkoop, A., De Ruiter, C., Attema, J., Menke, A.L., Caspers, M.P.M., Radhakrishnan, S., and Salic, K. (2020). A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology. Cells, 9.","DOI":"10.3390\/cells9092014"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e22435","DOI":"10.1096\/fj.202200111R","article-title":"Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr\u2212\/\u2212.Leiden mice with manifest obesity-associated NASH","volume":"36","author":"Gart","year":"2022","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/hep.26661","article-title":"Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease","volume":"59","author":"Moylan","year":"2014","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1053\/j.gastro.2016.05.051","article-title":"Comparison of Gene Expression Patterns between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues from Patients","volume":"151","author":"Teufel","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1152\/ajpgi.00145.2011","article-title":"Fast food diet mouse: Novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition","volume":"301","author":"Charlton","year":"2011","journal-title":"Am. J Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.jhep.2008.02.011","article-title":"Fructose consumption as a risk factor for non-alcoholic fatty liver disease","volume":"48","author":"Ouyang","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1002\/hep.23535","article-title":"Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease","volume":"51","author":"Abdelmalek","year":"2010","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Maeso-D\u00edaz, R., Boyer-Diaz, Z., Lozano, J.J., Ortega-Ribera, M., Peralta, C., Bosch, J., and Gracia-Sancho, J. (2019). New Rat Model of Advanced NASH Mimicking Pathophysiological Features and Transcriptomic Signature of the Human Disease. Cells, 8.","DOI":"10.3390\/cells8091062"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1038\/s41598-022-06205-8","article-title":"Relationship between the dynamics of non-alcoholic fatty liver disease and incident diabetes mellitus","volume":"12","author":"Han","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101102","DOI":"10.1016\/j.molmet.2020.101102","article-title":"GLP-1 receptor agonists in the treatment of type 2 diabetes\u2014State-of-the-art","volume":"46","author":"Nauck","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e133429","DOI":"10.1172\/jci.insight.133429","article-title":"Semaglutide lowers body weight in rodents via distributed neural pathways","volume":"5","author":"Gabery","year":"2021","journal-title":"JCI Insight"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1111\/cts.13235","article-title":"Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH","volume":"15","author":"Veidal","year":"2022","journal-title":"Clin. Transl. Sci."},{"key":"ref_34","first-page":"496","article-title":"Safety of Semaglutide","volume":"12","author":"Smits","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1007\/s00125-017-4289-0","article-title":"Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: A randomised, double-blind, placebo-controlled trial","volume":"60","author":"Kapitza","year":"2017","journal-title":"Diabetologia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jhep.2015.08.038","article-title":"Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis","volume":"64","author":"Armstrong","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.2337\/dc19-0883","article-title":"Oral Semaglutide Versus Empagliflozin in Patients with Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial","volume":"42","author":"Rodbard","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/bph.12490","article-title":"Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration","volume":"171","author":"Wang","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","first-page":"844","article-title":"The GLP-1 Analogs Liraglutide and Semaglutide Reduce Atherosclerosis in ApoE -\/- and LDLr -\/- Mice by a Mechanism That Includes Inflammatory Pathways","volume":"3","author":"Rakipovski","year":"2018","journal-title":"JACC"},{"key":"ref_40","first-page":"S10","article-title":"Semaglutide 2.4 mg once weekly improved liver and metabolic parameters, and was well tolerated, in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial","volume":"77","author":"Loomba","year":"2022","journal-title":"J. Hepatol. Int. Liver Congr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hep.21006","article-title":"Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob\/ob mice","volume":"43","author":"Ding","year":"2006","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1002\/hep.23569","article-title":"Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway","volume":"51","author":"Gupta","year":"2010","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33509","DOI":"10.1074\/jbc.M109.017608","article-title":"Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process","volume":"284","author":"Aviv","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1055\/s-0030-1253421","article-title":"GLP-1 (9-36) amide metabolite suppression of glucose production in isolated mouse hepatocytes","volume":"42","author":"Tomas","year":"2010","journal-title":"Horm. Metab. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1210\/en.2012-1937","article-title":"GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-\/-) mice","volume":"154","author":"Panjwani","year":"2013","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight Loss through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jacobs, S.A.H., Gart, E., Vreeken, D., Franx, B.A.A., Wekking, L., Verweij, V.G.M., Worms, N., Schoemaker, M.H., Gross, G., and Morrison, M.C. (2019). Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-\/-.Leiden Mice. Nutrients, 11.","DOI":"10.3390\/nu11081861"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3758\/BF03203630","article-title":"GPOWER: A general power analysis program","volume":"28","author":"Erdfelder","year":"1996","journal-title":"Behav. Res. Methods Instrum. Comput."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.ATV.0000067702.22390.20","article-title":"Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein","volume":"23","author":"Post","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-pathol-121808-102132","article-title":"Nonalcoholic fatty liver disease: Pathology and pathogenesis","volume":"5","author":"Tiniakos","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1194\/jlr.RA119000419","article-title":"Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice","volume":"61","author":"Pouwer","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/HJH.0b013e32834ddd8e","article-title":"Aliskiren inhibits atherosclerosis development and improves plaque stability in APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin","volume":"30","author":"Havekes","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/eurheartj\/ehu319","article-title":"Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin","volume":"36","author":"Simic","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:32:15Z","timestamp":1760124735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/8494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,9]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24108494"],"URL":"https:\/\/doi.org\/10.3390\/ijms24108494","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,9]]}}}